The goal of this proposal is to upgrade the High Throughput (HTP) Crystallization Laboratory at the Hauptman-Wooodward Medical Research Institute (HWl). Structural genomics and structural biology have both moved toward HTP methods for three-dimensional X-ray crystal structure determination. These structures are used as tools for understanding the relationship between the structure and function of molecular interactions and provide invaluable information for rational drug design. The identification of crystallization conditions is a prerequisite for success. The capacity to rapidly execute and analyze a large number of experiments under a wide range of solution conditions increases the likelihood of successful crystallization. The HTP Crystallization Lab has the capacity to set up and record results for microbatch crystallization experiments held in 1536-well microassay plates. The requested upgrade is for a key piece of equipment used to set up these experiments: the liquid handling system (LHS). Apogent Discoveries (formerly Robbins Scientific) Hydra 96 and Hydra 384 LHSs are currently in use to deliver oil, crystallization cocktail solutions, and protein solutions to 1536-well microassay plates for HTP crystallization. The upgrade is for the purchase of an Apogent Discoveries Tango LHS. The Tango is sufficiently similar in design and operation to the Hydra that it will efficiently integrate into the structure of the lab. It offers a fully automated platform for plate delivery and much faster deliveries. This will reduce the time required for technical oversight of the crystallization setups; increase the capacity of the facility; allow us to set up more samples/day. In cases where the sample is in limited supply, the Tango will set up crystallization plates using 42% less protein. We have identified an internal advisory committee to help the principal investigator with matters relevant to the scientific administration of the High Throughput Laboratory. The committee will insure the following user groups are equitably served: structural biology-900/yr, structural genomics-800/yr, and pharma-300/yr